Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLr−/− ApoB100/100 mice

Laís R. Perazza, Patricia L. Mitchell, Benjamin A.H. Jensen, Noëmie Daniel, Marjorie Boyer, Thibault V. Varin, Rihab Bouchareb, Renato T. Nachbar, Michaël Bouchard, Mylène Blais, Andréanne Gagné, Philippe Joubert, Gary Sweeney, Denis Roy, Benoit J. Arsenault, Patrick Mathieu, André Marette

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background and aims: Poor dietary habits contribute to the obesity pandemic and related cardiovascular diseases but the respective impact of high saturated fat versus added sugar consumption remains debated. Herein, we aimed to disentangle the individual role of dietary fat versus sugar in cardiometabolic disease progression. Methods: We fed pro-atherogenic LDLr−/− ApoB100/100 mice either a low-fat/high-sucrose (LFHS) or a high-fat/low-sucrose (HFLS) diet for 24 weeks. Weekly body weight gain was registered. 16S rRNA gene-based gut microbial analysis was performed to investigate gut microbial modulations. Intraperitoneal insulin (ipITT) and oral glucose tolerance test (oGTT) were conducted to assess glucose homeostasis and insulin sensitivity. Cytokines were assessed in fasted plasma, epididymal white adipose tissue and liver lysates. Heart function was evaluated by echocardiography. Aortic atheroma lesions were quantified according to the en face technique. Results: HFLS feeding increased obesity, insulin resistance and dyslipidemia compared to LFHS feeding. Conversely, high sucrose consumption decreased gut microbial diversity while augmenting inflammation and the adaptative immune defense against metabolic endotoxemia and reduced macrophage cholesterol efflux capacity. This led to more severe cardiovascular complications as revealed by remarkably high level of atherosclerotic lesions and the early development of cardiac dysfunction in LFHS vs HFLS fed mice. Conclusions: We uncoupled obesity-associated insulin resistance from cardiovascular diseases and provided novel evidence that dietary sucrose, not fat, is the main driver of metabolic inflammation accelerating severe atherosclerosis in hyperlipidemic mice.

Original languageEnglish
Pages (from-to)9-21
Number of pages13
JournalAtherosclerosis
Volume304
DOIs
StatePublished - Jul 2020
Externally publishedYes

Keywords

  • CVD
  • Fat
  • Inflammation
  • Insulin resistance
  • Obesity
  • Sugar

Fingerprint

Dive into the research topics of 'Dietary sucrose induces metabolic inflammation and atherosclerotic cardiovascular diseases more than dietary fat in LDLr−/− ApoB100/100 mice'. Together they form a unique fingerprint.

Cite this